Melatonin (N-acetyl-5-methoxytryptamine), which is a hormone synthesized and secreted principally in the pineal gland, increases in dark environments and decreases in light environments. Melatonin acts suppressively on pigment cells and the female gonads, and acts as a synchronous factor of biological clock while taking part in transmittance of photoperiodic code. Therefore, melatonin is expected to be usable for the treatment of diseases related to melatonin activity, such as reproductive and endocrinic disorders, sleep-awake rhythm disorders, jet-lag syndrome, various disorders related to aging and the like. It has been clarified that the production amount of melatonin decreases with aging and there is a report documenting that retention of the production amount of melatonin could prevent aging itself [Ann. N. Y. Acad. Sci., vol. 719, pages 456-460, (1994) (non-patent document 1)]. However, since melatonin is easily metabolized by metabolic enzymes in vivo [Clinical Examinations, vol. 38, No. 11, pages 282-284 (1994) (non-patent document 2)]. Therefore, melatonin is not entirely suitable as a drug.
WO 98/25606 (patent document 1) describes a compound represented by the formula
wherein Q1 and Q2 are each independently hydrogen or halogen; X is CH2, CH or oxygen; Y is CR3, CR3R4 or (CH2)n; n is 1-4; Z is CH2, CH or oxygen; R is hydrogen, halogen or C1-4 alkyl in both cases; m is 1 or 2; R1 is C1-6 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl, C1-6 alkylamino, C2-6 alkenyl, C1-6 alkoxy(C1-4)alkyl, C1-4 alkylthio(C1-4)alkyl or C1-4 trifluoromethylalkyl; R2 is hydrogen or C1-4 alkyl; and R3 and R4 are each independently hydrogen or C1-4 alkyl, or a pharmaceutically acceptable solvate thereof and the like, which is useful as a melatonergic agent.
US 2003/0216456 (patent document 2) describes a compound represented by the formula
wherein A is C1-4 alkylene or 1,2 disubstituted cyclopropyl; B is C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy or C1-4 alkylamino; X is hydrogen, halogen, C2-4 alkenyl, C1-6 alkyl, furyl, or phenyl optionally substituted with halogen, C1-6 alkoxy or haloalkyl; and Y is hydrogen, phenyl, or C1-6 alkyl optionally substituted with phenyl, or a salt thereof or a pharmaceutically acceptable solvate thereof and the like, which is useful as a melatonergic agent.
Bioorg. Med. Chem. Lett. 2004, vol. 14, pages 1197-1200 (non-patent document 3) describes a compound represented by the formula
wherein R is Ph(CH2)4 etc., and R1 is Et etc., and the like, as a melatonergic ligand.
U.S. Pat. No. 6,569,894 (patent document 3) describes a compound represented by the formula
wherein R1 and R2 are each hydrogen or halogen; R3 is hydrogen or C1-4 alkyl; R4 is C1-4 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl, C2-6 alkenyl, C1-4 alkoxy, C1-2 trifluoromethylalkyl or C1-4 alkylamino; R5 is hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy; Y is hydrogen or halogen; W is ethylene or 1,2 disubstituted cyclopropyl; m is 1 or 2; and n is 1-9, and the like, which is useful as a melatonergic agent.
Bioorg. Med. Chem. Lett. 2004, vol. 14, pages 3799-3802 (non-patent document 4) describes a compound represented by the formula
wherein R is Me etc., and R1 is Et, c-Pr etc., and the like, as a melatonin receptor agonist.
WO 99/62515 (patent document 4) describes a compound represented by the formula
wherein R1 and R2 are each independently hydrogen or halogen; X is CH2, CH or oxygen; Y is CR5, CR5R6 or (CH2)n; n is 1-2; Z is CH2, CH or oxygen; m is 1 or 2; R3 is hydrogen or C1-4 alkyl; R4 is C1-6 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl, C2-6 alkenyl, C1-4 alkoxy(C1-4)alkyl, C1-4 alkylthio(C1-4)alkyl or C1-4 trifluoromethylalkyl; and R5 and R6 are each independently hydrogen or C1-4 alkyl, or a pharmaceutically acceptable solvate thereof and the like, which is useful as a melatonergic agent.
WO 97/32871 (patent document 5) and U.S. Pat. No. 6,034,239 (patent document 6) disclose a compound represented by the formula:
wherein R1 represents an optionally substituted hydrocarbon group, optionally substituted amino or an optionally substituted heterocyclic group; R2 represents a hydrogen atom or an optionally substituted hydrocarbon group; R3 represents a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X represents CHR4, NR4, O or S wherein R4 represents a hydrogen atom or an optionally substituted hydrocarbon group; Y represents C, CH or N, provided that when X is CH2, Y is C or CH;
 is a single bond or a double bond,
ring A represents an optionally substituted 5- to 7-membered oxygen-containing heterocyclic ring; ring B represents an optionally substituted benzene ring; and m represents an integer of 1 to 4, or a salt thereof and the like, which has an affinity for melatonin receptor and is useful as a therapeutic agent for sleep disorder and the like.    patent document 1: WO 98/25606    patent document 2: US 2003/0216456    patent document 3: U.S. Pat. No. 6,569,894    patent document 4: WO 99/62515    patent document 5: WO 97/32871    patent document 6: U.S. Pat. No. 6,034,239    non-patent document 1: Ann. N. Y. Acad. Sci., vol. 719, pages 456-460, 1994    non-patent document 2: Clinical Examinations, vol. 38, No. 11, pages 282-284, 1994    non-patent document 3: Bioorg. Med. Chem. Lett. 2004, vol. 14, pages 1197-1200    non-patent document 4: Bioorg. Med. Chem. Lett. 2004, vol. 14, pages 3799-3802